12-51310050-A-G

Variant names:

• chr12-51310050-A-G
• rs766903
• NM_016293.4:c.162+3773T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016293.4(BIN2):​c.162+3773T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,202 control chromosomes in the GnomAD database, including 2,854 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2854 hom., cov: 32)
• Consequence: BIN2 NM_016293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 11 publications found

Genes affected

BIN2 (HGNC:1053): (bridging integrator 2) Enables phospholipid binding activity. Involved in several processes, including phagocytosis, engulfment; plasma membrane tubulation; and podosome assembly. Located in plasma membrane and podosome. Colocalizes with phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIN2	NM_016293.4	c.162+3773T>C		intron_variant	Intron 2 of 12	ENST00000615107.6	NP_057377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIN2	ENST00000615107.6	c.162+3773T>C		intron_variant	Intron 2 of 12	1	NM_016293.4	ENSP00000483983.2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28789 AN: 152084 Hom.: 2844 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.189 AC: 28827 AN: 152202 Hom.: 2854 Cov.: 32 AF XY: 0.190 AC XY: 14149 AN XY: 74408

African (AFR) AF: 0.230 AC: 9538 AN: 41512

American (AMR) AF: 0.203 AC: 3105 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3468

East Asian (EAS) AF: 0.148 AC: 768 AN: 5186

South Asian (SAS) AF: 0.237 AC: 1144 AN: 4824

European-Finnish (FIN) AF: 0.175 AC: 1856 AN: 10592

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11180 AN: 68016

Other (OTH) AF: 0.176 AC: 373 AN: 2116

Alfa AF: 0.177 Hom.: 4661

Bravo AF: 0.193

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766903; hg19: chr12-51703834;